Biomarkers: Key Indicators in Cardiovascular Health and Disease" – Highlights Their Diagnostic Nature

Abstract

Stroke continues to be a major global health challenge, with India bearing a significant share of the associated mortality and disability. India reports approximately 185,000 new stroke cases annually, equating to one stroke every 40 seconds and one stroke-related death every four minutes, while stroke incidence is higher among older adults, there is a notable increase in cases among younger individuals, including those under 40 years of age. Numerous risk factors, including as diabetes, hypertension, tobacco use, dyslipidaemia, and changes in lifestyle brought on by fast urbanisation and socioeconomic shifts, are responsible for this high burden. There are various kinds of cardiac strokes, with ischaemic strokes making up roughly one-third of haemorrhagic strokes. Heart strokes, encompassing both ischemic and haemorrhagic events, remain a leading cause of morbidity and mortality worldwide. Early diagnosis and timely therapeutic interventions are crucial for improving outcomes. In recent years, the role of biomarkers has gained significant attention for their potential in the early detection, risk stratification, prognosis, and monitoring of therapeutic responses in stroke patients. This review explores the current and emerging biomarkers associated with heart stroke, highlighting their roles, limitations, and future potential in advancing stroke management and personalized medicine.

Keywords

Introduction

Stroke remains one of the leading causes of death and long-term disability worldwide. Among the subtypes, cardioembolic strokes—caused by emboli originating from the heart—are particularly severe and account for 20–30% of ischemic strokes. The timely diagnosis and differentiation of stroke types are critical to initiating effective treatment. Biomarkers, which are measurable indicators of biological states or conditions, have become increasingly valuable in improving clinical decision-making in heart stroke scenarios. ^[1] Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, with acute coronary syndromes (ACS) and heart failure comprising a significant portion of this burden. In the realm of cardiology, early and accurate diagnosis is essential for effective treatment and improved patient outcomes. ^[2] One of the most critical advancements in this domain has been the identification and utilization of cardiac biomarkers—molecules released into the blood in response to cardiac stress or injury.These biomarkers have become indispensable tools in the diagnosis, risk stratification, prognosis, and monitoring of various cardiac conditions.  Cardiac biomarkers are substances that are released into the bloodstream when the heart is damaged or stressed. The most commonly used and clinically significant biomarkers include troponins (I and T), creatine kinase-MB (CK-MB), B-type natriuretic peptide (BNP) and its precursor NT-proBNP, myoglobin, and emerging markers like copeptin, heart-type fatty acid binding protein (H-FABP), and ST2. Among these, cardiac troponins have emerged as the gold standard for diagnosing myocardial infarction due to their high specificity and sensitivity for myocardial injury. ^[3] The clinical utility of cardiac biomarkers extends beyond diagnosis. They play a pivotal role in guiding therapeutic decisions, assessing the severity of heart disease, and predicting patient outcomes. For example, elevated BNP and NT-proBNP levels are commonly used to diagnose and evaluate the severity of heart failure, while serial measurements of troponins can help determine the extent of myocardial damage and the effectiveness of treatment strategies in acute coronary syndromes.^[4] With the continuous advancement in biomarker discovery and testing technologies, the scope of cardiac biomarkers is expanding. High-sensitivity assays and multi-marker approaches are enhancing the ability to detect cardiac injury earlier and more accurately. In this context, understanding the biological significance, kinetics, and clinical application of cardiac biomarkers is essential for clinicians, researchers, and healthcare professionals involved in the management of cardiovascular diseases.

Pathophysiology of Cardiovascular diseases

Cardiovascular diseases (CVDs) encompass a broad spectrum of disorders that affect the heart and blood vessels, including coronary artery disease (CAD), heart failure, arrhythmias, hypertension, and cerebrovascular diseases. Collectively, they are the leading cause of death globally, accounting for millions of deaths each year. Understanding the pathophysiology of cardiovascular diseases is crucial for developing effective prevention strategies, diagnostic tools, and treatment modalities. At the core of many CVDs lies a complex interplay between genetic, environmental, metabolic, and behavioural factors that lead to progressive structural and functional changes in the cardiovascular system. ^[5] The pathophysiology of cardiovascular diseases often begins with endothelial dysfunction, a condition where the inner lining of blood vessels loses its normal regulatory functions. This dysfunction is typically triggered by risk factors such as hypertension, hyperlipidemia, diabetes, smoking, and chronic inflammation. As endothelial integrity deteriorates, it becomes more permeable to lipids and white blood cells, promoting the development of atherosclerosis—the accumulation of lipid-laden plaques within arterial walls. Over time, these plaques can rupture, leading to thrombus formation and potentially causing myocardial infarction or stroke. ^[6] Another critical component in the pathophysiology of CVD is cardiac remodeling, which involves structural changes in the heart’s size, shape, and function in response to chronic pressure or volume overload, as seen in hypertension or valvular heart disease. These changes can lead to heart failure, characterized by impaired pumping ability and inadequate perfusion of tissues and organs. Furthermore, neurohormonal activation, particularly the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, plays a major role in the progression of cardiovascular diseases. Chronic activation of these systems leads to vasoconstriction, sodium and water retention, and myocardial fibrosis, all of which exacerbate heart and vascular dysfunction. In summary, the pathophysiology of cardiovascular diseases is multifaceted and dynamic, involving a cascade of events that affect vascular tone, cardiac function, and systemic homeostasis. ^[7] A thorough understanding of these mechanisms is essential for advancing clinical interventions and improving cardiovascular health outcomes. Heart strokes often result from conditions like atrial fibrillation (AF), valvular heart disease, myocardial infarction, or left ventricular thrombi, Patent foramen ovale (PFO). These conditions lead to the formation of emboli, which travel through the circulation and block cerebral vessels, resulting in ischemic stroke. The associated systemic and localized responses—such as inflammation, neuronal injury, and coagulation—trigger changes in blood-borne biomarkers that can be quantified and utilized clinically. ^[8]

Fig 1: Pathophysiology of Heart Stroke

Risk factors

Several risk factors like diabetes mellitus, heart disease, dyslipidemia, alcohol, consumption, drug abuse, hypertension, and smoking are established contributors Furthermore, a variety of unknown social and cultural factors have a major impact on the disease process, as evidenced by changes in lifestyle and economic growth in India that is readily observable. In India, diabetes, smoking, hypertension, and dyslipidaemia are the main modifiable risk factors for stroke. ^[9]

Fig 2: Risk factors for Heart Stroke

Diagnostic Strategies  

CT scan: To differentiate ischemic from haemorrhagic stroke

MRI: Superior in detecting early ischemic changes

CT/MR angiography: Evaluates cerebral vasculature ^[10]

Cardiac Evaluation

Echocardiography: Identifies intracardiac thrombi or PFO

• ECG/Holter monitoring: Detects atrial fibrillation
• Transesophageal echocardiography (TEE): Superior for evaluating cardiac sources of emboli
• Cardiac biomarkers

Biomarkers: Cardiac biomarkers are substances released into the blood when the heart is damaged or stressed. They are crucial for diagnosing heart conditions—especially acute coronary syndromes (like heart attacks). ^[11]

Types of Biomarkers in Stroke

 Diagnostic Biomarkers

Glial Fibrillary Acidic Protein (GFAP): Elevated in hemorrhagic stroke and contributes to the distinction between acute stroke patients experiencing ischaemic stroke (AIS) and intracerebral haemorrhage (ICH). Additionally, especially in ischaemic stroke, it exhibits promise as a biomarker for stroke severity and prognosis. Both AIS and ICH have higher amounts of GFAP, a brain-specific protein that is released into the circulation following brain tissue destruction. ^[12]

Neuron-Specific Enolase (NSE) and S100B: Indicators of neuronal damage; increased levels reflect blood-brain barrier disruption and infarct size. NSE and S100B are helpful in determining the degree of brain damage and forecasting outcomes in disorders such as stroke and traumatic brain injury because they are released into the bloodstream and cerebrospinal fluid following damage to neurones or glial cells. ^[13]

Matrix Metalloproteinases (MMPs): MMP-9 is particularly associated with blood-brain barrier breakdown in acute stroke. Increased levels of MMPs, especially MMP-9, have been linked to stroke and other neurological conditions, where they may be responsible for tissue damage and neuronal death. MMPs are also implicated in the breakdown of the extracellular matrix. ^[14]

Cardiac-Related Biomarkers

Cardiac Troponins (cTnT, cTnI): In the contractile apparatus of the heart muscle, cardiac troponins are essential regulatory proteins that contribute to muscle contraction by binding with calcium ions and preventing actin and myosin from connecting. They are a sensitive biomarker for detecting myocardial injury, particularly in cases like acute myocardial infarction (heart attack), since they are released into the circulation when the heart muscle is damaged. ^[15] Elevated troponin levels post-stroke may suggest underlying cardiac injury, often linked to atrial fibrillation or myocardial infarction.

B-type Natriuretic Peptide (BNP) and NT-proBNP: N-terminal proBNP (NT-proBNP) and B-type natriuretic peptide (BNP) are biomarkers that are mainly used to identify and track heart failure. They assist medical professionals in evaluating cardiac function, directing therapy, and forecasting results for heart failure patients. Increased concentrations of these peptides may be a sign of left ventricular dysfunction, severe diastolic dysfunction, or heart failure. Useful in identifying cardioembolic strokes and assessing stroke severity; high levels correlate with left atrial dysfunction and increased stroke risk in AF patients. ^[16]

Inflammatory and Coagulation Biomarkers

C-reactive protein (CRP): A non-specific marker of inflammation; elevated levels are associated with increased stroke severity and poor outcomes. ^[17]

Interleukins (IL-6, IL-1β) and TNF-α: Involved in systemic inflammatory response; higher concentrations are linked to larger infarcts and poor prognosis. ^[18]

D-dimer: Elevated levels suggest active coagulation and fibrinolysis; useful in predicting stroke in patients with AF or thrombosis. ^[19]

 Emerging Biomarkers

 MicroRNAs (miRNAs)

Small non-coding RNAs like miR-124, miR-210, and miR-21 are emerging as potential biomarkers due to their role in regulating gene expression during ischemic events. They show promise in differentiating stroke subtypes and predicting recovery outcomes. ^[20]

Exosomal Marker

Exosomes are tiny vesicles released by cells and also act as intercellular messengers and possible biomarkers in cardiovascular, endothelial dysfunction, myocardial damage and stroke disorders. They may transport a variety of substances, including lipids, proteins, mRNAs, and miRNAs and nucleic acids, which might affect cell behaviour and possibly help with diagnosis and treatment. Their content changes during stroke and may provide insight into neuroinflammatory and neuroprotective processes. Additionally, they might have therapeutic promise by serving as vectors for the targeted delivery of treatments, including protective miRNAs. ^[21]

Fig.3: Cardiac Biomarkers

Metabolomics and Proteomics:

Metabolomic profiling reveals changes in amino acids, lipids, and energy metabolism during stroke. For instance, decreased arginine and increased lactate levels can indicate ischemic damage. Proteomic technologies are uncovering novel stroke-associated proteins for diagnostic use. ^[22]

Emerging biomarkers provide diagnostic and prognostic value:

•   Cardiac troponins: Elevated in stroke with cardiac stress

•   BNP/NT-proBNP: Indicates cardioembolic source

•   CRP, IL-6: Mark systemic inflammation

•   S100B, GFAP: Indicate neuronal/glial damage

Table 1: Biomarkers and its use

CONCLUSION

Cardiac biomarkers play a critical role in the early diagnosis, risk stratification, and management of cardiovascular diseases, particularly acute coronary syndromes. Among these, troponins remain the gold standard for detecting myocardial injury due to their high specificity and sensitivity. Other markers, such as CK-MB, BNP, and NT-proBNP, provide valuable complementary information regarding cardiac function and heart failure. The ongoing development of novel biomarkers and high-sensitivity assays continues to enhance clinical decision-making, enabling more precise and timely interventions. Ultimately, the integration of cardiac biomarkers with clinical assessment and imaging improves patient outcomes and guides therapeutic strategies.

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